Spectrum | Autism Research News

Social attention shifts differently over time for autistic adults

Fri, 23 Oct 2020 11:00:00 GMT

When autistic and non-autistic people look at photographs depicting social scenes, they generally look at faces first and then let their eyes wander to other parts of the image. After a few seconds, neurotypical adults are likely to return their gaze to the faces, but autistic people are not, according to a new eye-tracking study¹.

The findings may help explain why people with autism tend to spend less time overall looking at faces than non-autistic people do: It’s not that they are uninterested in faces, but that social stimuli may not capture their attention in the same way.

Previous studies have examined how certain factors, such as a person’s ability to learn from or process different stimuli, affect social attention in autism, but few have evaluated how ‘looking patterns’ change over the course of an experiment or with age.

“This study goes a long way towards us having some insight into that process,” says Rebecca Shaffer, associate professor of pediatrics at Cincinnati Children’s Hospital in Ohio, who was not involved in the study.

Based on their eye movements, neurotypical people seem to grow more interested in faces as they age, but autistic people do not, the researchers found. And the autistic people who had the most distinct pattern of eye movements also had the poorest communication skills.

The results show that “there is information to be gained” by analyzing eye-tracking data in this way, says lead investigator Emily Jones, professor of translational neurodevelopment at Birkbeck, University of London in the United Kingdom.

Social scenes:

Jones and her colleagues collected eye-tracking data from 650 autistic and non-autistic people aged 6 to 30 years taking part in the Longitudinal European Autism Project (LEAP), a multi-country effort to identify biomarkers for autism.

Researchers at six sites used an eye tracker to follow the participants’ gaze as they viewed a series of six randomly ordered photographs of social scenes — children playing or an adult interacting with a child and a toy, for example — on a computer screen for 20 seconds each. For each second, the researchers measured the proportion of time a participant spent looking at social elements of the photograph, such as a person’s face, head or hair, versus other parts of the scene, and they calculated how that ratio changed over time. They also examined how these looking patterns vary by age.

Autistic people of all ages are just as likely as their non-autistic peers to look at faces at the start of each trial, the researchers found, confirming previous findings that autism does not affect someone’s ability to detect and orient to faces².

But as time passed, the groups differed in where they looked: After scanning other elements of a scene, neurotypical adults ultimately returned their attention to the faces, whereas neurotypical children and autistic people of all ages were less likely to do so. The study was published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging in September.

The results suggest that two different mechanisms drive the early and late looking patterns, and autism affects only the latter, Jones says.

By looking at individual differences, Jones and her colleagues found that autistic people with the most atypical looking patterns had the poorest adaptive communication and socialization skills, as measured by a test called the Vineland Adaptive Behavior Scales.

Though preliminary, that finding suggests that better communicators are more likely to become “experts” at faces over time, and therefore are more likely to devote attention to faces as they age, says study investigator Teresa Del Bianco, a postdoctoral researcher at Birkbeck, University of London.

The idea that communication skills can alter patterns of social attention is in line with another 2020 study, which found that once toddlers begin learning how to talk, they change which parts of a face they focus on³.

Eyeing the future:

“The million-dollar question in our field is: Why? Why is selective attention, or top-down attention, in autism so poor when it comes to social stimuli, like faces?” says Katarzyna Chawarska, professor of child psychiatry at Yale University, who was not involved in the work.

Though the researchers hint at some answers, the study was limited by the fact that it is only observational, she says. It was not designed to test hypotheses that might explain the mechanisms at play.

Moving forward, Jones and Del Bianco plan to study whether there are any sex differences in the patterns of social attention for people with and without autism. They also want to use their eye-tracking analysis method on data collected from people viewing videos of social scenes, which will better replicate looking patterns in the real-world, Del Bianco says.

The post Social attention shifts differently over time for autistic adults appeared first on Spectrum | Autism Research News.

What it’s like to be a Black autism researcher

Thu, 22 Oct 2020 11:00:00 GMT

Autism research is an overwhelmingly white field — one in which Black researchers say they experience both overt and covert racism.

This summer took an especially heavy toll on many scientists of color as protests erupted in response to the deaths of George Floyd, Ahmaud Arbery, Breonna Taylor, Rayshard Brooks, Jacob Blake, Daniel Prude, and other victims of police violence.

Spectrum spoke with four Black women who are autism researchers — Mary Agyapong, Desi Jones, Cliona Kelly and Termara Parker — about their experiences leading up to and during this past summer, and what they hope will happen next.

You can read the transcript for this episode here.

The post What it’s like to be a Black autism researcher appeared first on Spectrum | Autism Research News.

Cell maps reveal diversity of neurons in gut

Wed, 21 Oct 2020 11:00:00 GMT

A new atlas details gene expression in neurons and other cells from the intestines of mice and people¹.

About 40 percent of children with autism or other developmental conditions have gastrointestinal issues, for which researchers have proposed many explanations. Some studies suggest that mutations in genes linked to autism affect neurons in the gut.

In the new work, researchers profiled gene expression in 5,068 mouse and 1,445 human gut neurons, described in September in Cell. By mapping potential interactions between gut neurons and other cells in the colon, they highlight many links between gut neurons and immune cells.

In addition, the team identified several genes linked to autism and other conditions expressed in human gut neurons. Autism-linked genes, such as NRXN1, ANK2 and DSCAM, are expressed at higher levels in gut neurons than in other cell types in the colon, which may help explain why gut problems often accompany autism, the researchers say.

mRNA boost:

Researchers typically examine gene expression in individual cells by plucking the cells — or their nuclei — from tissue and sequencing the messenger RNA (mRNA), the intermediary between genes and proteins, contained within. But this approach is tricky with gut neurons because the cells are rare, fragile and tightly intertwined with surrounding tissues. Also, traditional approaches for isolating nuclei may leave too little mRNA intact for analysis, the researchers say.

To overcome these challenges, the researchers developed a new, gentle method for breaking apart cells in tissue and isolating nuclei. The technique, called RAISIN, leaves the outer membrane surrounding the nucleus and the ribosomes attached to it intact. Because ribosomes translate mRNA into proteins, collecting them too boosts the amount of mRNA available for analysis.

The researchers used RAISIN to tease out cell nuclei in gut tissue samples from 29 mice. The animals were engineered to express fluorescent proteins in their gut neurons and glia, cells that support and communicate with neurons. The researchers then used standard methods to isolate individual fluorescently labeled nuclei and sequence their mRNA.

They used this information to create an atlas of gene expression, classifying 21 types of neurons and three types of glia in the mouse gut. The atlas also reveals gene expression patterns that vary according to age, sex, gut region and time of day.

Sorting cells:

The team developed another method, called MIRACL-seq, to sort and analyze isolated nuclei that cannot be fluorescently labeled, such as those from people.

MIRACL-seq is based on earlier droplet-based approaches that separate nuclei into microscopic droplets containing DNA strands that bind to the mRNA and act as unique barcodes. Researchers can sequence each droplet’s mRNA, along with its attached barcode, to measure a cell’s gene expression.

Droplet-based approaches are generally inefficient for rare cell types, such as gut neurons. In the new study, however, researchers optimized MIRACL-seq to capture eight times as many nuclei per experiment as usual.

Using RAISIN and MIRACL-seq in tandem, the team examined colon and small intestine tissue from 10 additional mice, none of which expressed fluorescent proteins in gut neurons, and healthy colon tissue from 16 people with colorectal cancer. They used these data to refine their mouse atlas, to create a human atlas and to draw comparisons between the two.

The atlas could help researchers probe the diverse functions of the gut nervous system, the researchers say. It could also shed light on gut-brain connections.

The post Cell maps reveal diversity of neurons in gut appeared first on Spectrum | Autism Research News.

Beyond the bench: A conversation with William Mandy

Tue, 20 Oct 2020 11:00:00 GMT

Whether they mean to or not, just about everyone these days is taking William Mandy’s advice for a successful academic career: Find time to work from home. Mandy, a clinical psychologist and professor of clinical psychology at University College London, works in the United Kingdom’s most populous city but endures a train-bike-walk commute each day so that he can live in a quieter place — or at least he did pre-pandemic.

Now Mandy splits his time between teaching math and history to his 6- and 9-year-old children and managing his research team remotely, meaning life is both simpler and more complicated than before. When a problem gets particularly thorny, he says, one strategy remains nearly foolproof: a walk in the woods with his dog.

Spectrum spoke with Mandy about the golden hours for writing and why — when there isn’t a pandemic — he likes attending conferences in new parts of the world.

Spectrum: What are you working on right now?

William Mandy: The main thing I and my collaborators and my group are working on is various questions focused around autism and sex and gender. We’re really interested in whether there are important differences in the experiences and characteristics of autistic girls and women compared with autistic boys and men, and thinking about how that plays out in terms of their lives, their needs and so on.

For example, that’s led us into becoming interested in the overlap between autism and anorexia nervosa. There’s growing evidence that autistic women compared with non-autistic women have an elevated risk of developing anorexia. We’re interested in why that is and hoping to use the insights we gain from that, maybe five years down the line, to start developing better services for autistic women with serious eating problems.

Another thing that came out of our interest in sex and gender differences was camouflaging — this idea that many autistic people often feel compelled to develop a whole range of strategies to mask their autism. There’s growing evidence from our group and from others that autistic people who camouflage more also tend to have higher rates of mental health difficulties, so we’re really intrigued as to whether there’s any kind of causal relationship there and whether we could use insights from camouflaging to develop interventions that allow autistic people to live happier, more satisfying lives.

S: What does your day look like?

WM: I live a little bit outside of London but work in London, so my normal, pre-coronavirus day started with a train ride and me sitting there with my laptop, tapping away at the keyboard, trying to answer as many emails as possible before my train gets to Paddington Station, at which point I get on my folding bicycle and cycle across London to where I work at University College London. I work not just in autism research but also in helping to train clinical psychologists, so often my day is spent in meetings about running a course. Often my favorite bit is meeting with Ph.D. students and helping them think through what they’re going to do next or problem-solve around what they’re doing. And then it’s back on the folding bike, back across London, back to Paddington and back on the train, and then that very nice feeling of stepping off the train into a nice, pleasant village and leaving the hustle and bustle of London behind.

Now, during the pandemic, there’s normally a negotiation that goes on with my wife in the morning about who’s going to do what elements of schooling. She’s definitely become the head teacher and I seem to be the maths teacher. It’s about kind of balancing a whole load of meetings on Microsoft Teams and Zoom with trying to keep one’s research going, but also looking after and educating the kids. I’ve really quite enjoyed the experience of taking more of a role in my children’s education. I’ve certainly learned quite a lot about the Vikings in the past couple of weeks that I wouldn’t have known otherwise.

S: When and where are you most productive?

WM: The one tip I give to anyone looking to do an academic career is you must work from home on a regular basis, and that’s where I do all of my writing and thinking. I’m generally at my best first thing in the morning. I normally have three or four good hours where I can really focus and produce things. When I work at home, I try to structure it so I don’t waste those good hours on emails or things like that. I use them for writing, whether it’s papers or grant applications or whatever, and then once the light has faded slightly on my concentration after lunch, I try to stack in a bunch of tasks that are easier to be pulled along by. So at home in my little office before lunch is when I’m most productive.

S: What’s your favorite conference to attend?

WM: In June 2019, I went to Singapore to the Asia Pacific Autism Conference, which I hadn’t been to before. That was great, partly because it’s just so exciting being in Southeast Asia, and partly just because there was a whole different take on the autism world than I was used to. It felt like a very practically focused conference. It was very respectful to autistic people. For example, at the closing ceremony, there was an absolutely awesome band of all autistic people, and there were lots of roles within the conference for autistic people. It didn’t feel just tokenistic.

S: What are you reading right now?

WM: One of the nice things about the lockdown is I am doing a bit more reading than I used to. I’m reading the Hilary Mantel series, with “Wolf Hall” and “Bring Up the Bodies.” I’m just about to start the third one, about Thomas Cromwell in Henry VIII’s court. I’m rather enjoying the escapism of such a well-crafted historical novel.

In terms of academic reading, once you get to a certain point in academia you read huge amounts of text, but you mostly do it in this very functional way. In my role as a journal editor or a supervisor of students, I read a lot of drafts and manuscripts, which is good because it helps me stay attuned to the all the different developments in the field or just get a sense of what people are up to.

S: Do you subscribe to any journals or magazines in print?

WM: The London Review of Books is the only one. These days, everything is electronic, so I have particular journals that I like. Obviously Autism, the journal of which I’m an editor, is my favorite journal, and I also completely enjoy the Journal of Child Psychology and Psychiatry. I always find there’s really interesting stuff in there.

S: Are you active on social media?

WM: I am. I’m on Twitter. I’m quite a cautious Twitter user. It’s been a long time since I had a Twitter beef with anybody. I’m getting more to just using it to take the temperature in a way, especially being interested in what autistic people and fellow researchers are saying and as a way to let the world know about our research and to hear what people think of it.

I think I learned early on that there’s no real discourse to be had on Twitter. It’s not a place in which people’s minds are changed and shaped by interesting ideas. It’s more a place where people just output.

S: What do you eat or drink while you’re working?

WM: It is a stereotype, but it is true that the English are obsessed with tea. I drink a lot of tea, as I’m drinking it now. In the mornings I’m fueled by coffee and then I convert to tea at about lunchtime, and that keeps me going through the day.

S: How many unread emails are in your inbox right now?

WM: Let’s have a look. Okay, this is about par: There are 89. Anything over 100 and I start to get jittery, but 89 I can just about live with.

The post Beyond the bench: A conversation with William Mandy appeared first on Spectrum | Autism Research News.

Immune markers in newborns show complex relationship with autism odds

Mon, 19 Oct 2020 11:00:00 GMT

Newborns with above- or below-average levels of C-reactive protein in their blood are more likely to be autistic than their peers, according to a new study¹. The babies’ odds of having autism also vary depending on how their immune system interacts with environmental factors, such as their mothers’ iron levels during pregnancy.

High levels of C-reactive protein might indicate an overly robust immune system, whereas low levels might indicate a relatively weak ability to fend off pathogens — either of which could boost the odds of autism in some children, says lead investigator Renee Gardner, a researcher at the Karolinska Institutet in Stockholm, Sweden.

The findings complicate a large body of evidence suggesting that increased inflammation, as part of an immune response in a pregnant woman or her child, raises the child’s likelihood of having autism, the investigators and other researchers say.

“They are supporting [the theory of] maternal inflammation, but at the same time they reveal a very complex picture,” says Lior Brimberg, assistant professor of neuroimmunology at the Feinstein Institute for Medical Research in Manhasset, New York, who was not involved in the research.

Past observational studies suggest that having an infection during pregnancy can significantly increase the odds of having an autistic child, as can giving birth during the cold-weather months, when cases of influenza rise. And stimulating the immune system of pregnant mice or monkeys can disrupt brain development in their babies.

But the new findings demonstrate that these exposures don’t occur in a vacuum, suggesting that the strength of an infant’s immune system can mediate how infections or other environmental threats influence her likelihood of having autism, Gardner says.

“The answer just seems to be more complex than what would be predicted,” she says.

The relationship between the immune system and brain development is particularly important for researchers to examine given the current coronavirus pandemic, says David Amaral, distinguished professor of psychiatry and behavioral sciences at the University of California, Davis MIND Institute, who was not involved in the work. Short-term spikes in autism diagnoses have been linked to past disease outbreaks, such as the 1960s Rubella epidemic in the United States².

“It’s not clear what’s going to happen [with COVID-19],” Amaral says. “I don’t want to frighten women who may be pregnant and be worried, but scientifically it’s an issue that we have to deal with.”

Protein levels:

To protect the body from pathogens, the immune system produces short-lived proteins called cytokines that can alert immune cells to attack invaders. Some cytokines also stimulate the production of C-reactive protein and other ‘acute-phase proteins,’ which tend to stay in the blood longer, making them a more reliable marker of past strong immune responses.

Using a Swedish birth registry, the researchers analyzed the levels of nine acute-phase proteins in dried blood spots taken three to five days after birth from 924 people with autism and 1,092 non-autistic people.

They also mined the birth records for data on factors associated with autism, including a mother’s age, socioeconomic status, psychiatric history and infection-related hospitalizations during pregnancy, as well as the child’s birth order and gestational age and size at birth.

On average, autistic children had higher levels of eight of the nine proteins than controls, the study found. And the odds of having autism were most strongly associated with levels of C-reactive protein: Infants with both higher and lower levels of it were more likely to have autism than their peers — a finding Gardner calls “unanticipated.” Among the infants with atypical levels of C-reactive protein, those with higher levels were more likely to have autism than those with lower levels.

The findings were published in Biological Psychiatry in September.

Autistic newborns whose mothers had been hospitalized for infections during late pregnancy had lower levels of most of the proteins than the other autistic babies. This pattern of protein levels was reversed among children without autism, suggesting that babies whose immune systems respond robustly to serious infections are less likely to be autistic.

Children whose mothers had anemia had a lower chance of being autistic if they had high levels of ferritin, a protein that helps the body ‘hide’ the iron that pathogens need to survive. The finding helps link a mother’s nutrition to the immune system and autism, Gardner says.

“It’s pulling in this whole other area,” she says.

They saw no connection between maternal body mass index and acute-phase proteins in children, undermining theories that inflammation explains the association between obesity during pregnancy and a child’s odds of having autism, Gardner says.

Complex relationship:

Gardner and her team also compared autistic children with 203 of their unaffected siblings and saw the opposite of what they observed in unrelated controls: On average, levels of six of the nine proteins were higher in the non-autistic siblings than in the children with autism.

The finding suggests that a strong immune response may help to counteract underlying vulnerabilities to autism — whether genetic or an environmental exposure in utero — that tend to be shared among siblings, the researchers say.

“That would actually really fly in the face of this whole immune activation hypothesis, where we think that inflammation is bad bad bad bad bad,” Gardner says.

Both the large size of the study and its use of the babies’ blood spots strengthen the findings, other researchers say. Much previous work has focused on immune markers in the mother or in older children.

If certain levels of acute-phase proteins or similar markers are found to be specific to autism, testing blood for such markers could be used as an early indicator of the condition, Amaral says. Blood spots are collected from nearly all babies in many countries around the globe.

“People are struggling to try and find early markers of risk for autism,” Amaral says. “If there could be indications in the blood spots which are routinely taken at or near birth, it would be a major boon.”

Gardner and her team are currently analyzing blood samples from some of the mothers in this cohort, as well as examining other markers in the babies’ blood, such as anti-gluten antibodies, to further understand the relationship between immunity, autism and factors such as nutrition.

The post Immune markers in newborns show complex relationship with autism odds appeared first on Spectrum | Autism Research News.

Traits in mothers may signal gene variants for autism

Fri, 16 Oct 2020 11:00:00 GMT

Autistic children’s traits track more with subtle, autism-like behaviors in their mothers than with those in their fathers, according to a new study¹.

In particular, autistic children whose mothers have problems with pragmatic language — communicating in social settings — tend to have especially prominent social-communication difficulties themselves, the study shows. What’s more, those mothers also have many common genetic variants linked to autism. These common variants are thought to account for as much as half of autism’s genetic basis.

The findings suggest that the same genetic factors that contribute to autism also underlie a collection of mild traits known as the ‘broad autism phenotype.’ The presence of these traits may be a sign that a woman carries a genetic predisposition to autism.

“I was really excited to see that features of broad autism phenotype, and especially language-related features, seem to be really important in understanding how genetic liability is expressed and really linked to molecular genetic variation,” says co-lead investigator Molly Losh, director of the Neurodevelopmental Disabilities Lab at Northwestern University in Evanston, Illinois.

Researchers have long noted that some parents show mild versions of the same traits seen in their autistic children. The new study investigated the relationship between the genetic propensity for autism and the expression of autism traits within families.

It shows that autism traits and expression of the condition’s genetics roots may differ for mothers and fathers, says co-lead investigator Lea Davis, assistant professor of genetic medicine at Vanderbilt University in Nashville, Tennessee.

The findings fit with a theory called the ‘female protective effect,’ which holds that it takes more genetic factors to lead to autism in women than it does in men. In this case, women who have mild traits of autism may pass down autism-related gene variants to their children, without having autism themselves.

Matching traits:

Davis, Losh and their colleagues drew on data from the Simons Simplex Collection, a repository of genetic and trait information from 2,621 children with autism and their parents. The children come from ‘simplex’ families, meaning those that have non-autistic parents and only one child with autism. (The repository is funded by the Simons Foundation, Spectrum’s parent organization.)

The researchers looked at a variety of data on the children’s autism traits, as measured by the Autism Diagnostic Observation Schedule (ADOS) and three questionnaires that parents fill out: the Autism Diagnostic Interview-Revised, the Social Responsiveness Scale and the Repetitive Behavior Scale-Revised. They also examined parents’ responses on the Broad Autism Phenotype Questionnaire (BAPQ) — a 36-item survey that assesses three autism-related traits: a rigid personality, social aloofness and problems with language.

Fathers scored higher than mothers did on the BAPQ overall, and also across all three traits. The fathers’ scores in the rigidity domain correlated with the children’s repetitive behaviors as measured by the parent-report questionnaires, whereas the mothers’ scores overall and in each domain tracked with the children’s language and social-communication difficulties.

The researchers then used genetic data to calculate each family member’s ‘polygenic score’ — the sum total of all gene variants tied to autism that are present in their DNA.

Mothers with high polygenic scores tend to have autism-related traits, especially pragmatic-language difficulties, the researchers found. By contrast, the fathers’ polygenic scores do not relate to their BAPQ scores. The work was published in September in Biological Psychiatry.

The study is one of the first to demonstrate the role of maternal characteristics and how a woman’s traits correlate with her child’s autism, says David Evans, professor of psychology and neuroscience at Bucknell University in Lewisburg, Pennsylvania, who was not involved in the study. Previous studies have been focused more on the link between a father’s broad autism phenotype and his child, he says.

The children’s ADOS scores do not correlate with their parents’ BAPQ scores, which was “surprising,” says Meghan Swanson, assistant professor of psychology at the University Texas at Dallas. “It will be difficult to determine if the investigators found this pattern of results because the ADOS is lacking in dimensionality or if the results are biased due to mothers’ being the primary informant for parent-report measures.”

Future female directions:

Future studies should investigate whether the mothers’ and fathers’ behaviors correlate more closely with those of their autistic daughters or sons, Evans says.

Understanding the parents better might teach researchers something about potential outcomes in their children, Swanson says.

Davis and Losh plan to carry out more studies of the broad autism phenotype, especially in women. This information might help researchers better identify what autism looks like in girls and women, Davis says.

“The field is really good at identifying these features at a granular level for young boys, really not nearly as good at doing that for, let’s say, adult women,” Davis says. “That’s another area that we’re just starting to scratch the surface on, and this was an interesting way of kind of looking at some of those questions.”

They also plan to study families that have more than one child with autism, because the findings from the simplex families may not apply to these multiplex families.

“Extending these sorts of analyses to the broader population of families, where genetic etiology is going to be much more heterogeneous, is an important next step,” Losh says.

The post Traits in mothers may signal gene variants for autism appeared first on Spectrum | Autism Research News.

Brain structure changes in autism, explained

Thu, 15 Oct 2020 11:00:00 GMT

Autism is a neurodevelopmental condition. Although it is diagnosed based on the presence of two core behaviors — restricted interests and repetitive behaviors, as well as difficulties with social interactions and communication — those traits are thought to arise because of alterations in how different parts of the brain form and connect to one another.

No research has uncovered a ‘characteristic’ brain structure for autism, meaning that no single pattern of changes appears in every autistic person. Studies of brain structure often turn up dissimilar results — there is great variety across individuals in general. But some trends have begun to emerge for subsets of autistic people. These differences might one day provide some insight into how some autistic people’s brains function. They may also point to bespoke treatments for particular subtypes of autism.

Here is what we know about how brain structure differs between people with and without autism.

Which brain regions are known to be structurally different between autistic and non-autistic people?
Studies that make use of a brain-scanning technique called magnetic resonance imaging (MRI) have highlighted a few brain regions that are structurally distinct in people with autism.

Children and adolescents with autism often have an enlarged hippocampus, the area of the brain responsible for forming and storing memories, several studies suggest, but it is unclear if that difference persists into adolescence and adulthood^1,2.

The size of the amygdala also seems to differ between people with and without autism, although researchers from different labs have turned up conflicting results. Some find that people with autism have smaller amygdalae than people without autism, or that their amygdalae are only smaller if they also have anxiety³. Others have found that autistic children have enlarged amygdalae early in development and that the difference levels off over time^2,4.

Autistic people have decreased amounts of brain tissue in parts of the cerebellum, the brain structure at the base of the skull, according to a meta-analysis of 17 imaging studies⁵. Scientists long thought the cerebellum mostly coordinates movements, but they now understand it plays a role in cognition and social interaction as well.

On a more global level, the cortex — the brain’s outer layer — seems to have a different pattern of thickness in people with and without autism. This difference tracks with alterations to a single type of neuron during development, a 2020 study suggests.

How do these structural differences change during development?
Some infants who are later diagnosed with autism have unusually fast growth in certain brain regions, according to multiple studies^6,7,8. Compared with their non-autistic peers, autistic children have significantly faster expansion of the surface area of their cortex from 6 to 12 months of age. In the second year of life, brain volume increases much faster in autistic children than in their non-autistic peers.

The results support earlier research that saw enlarged heads and brains in a fraction of autistic people: Their cortex seems to expand too quickly in infancy and early childhood, even before autism traits can be detected behaviorally. During late childhood, neurotypical brains continue to grow in size; in adulthood, they begin to shrink. By contrast, the brains of some people with autism start to shrink prematurely, before their mid-20s.

Some children who are later diagnosed with autism also have excess cerebrospinal fluid — the liquid that surrounds the brain — compared with their non-autistic peers, which may contribute to having an enlarged head. Those with the most fluid tend to also have the most prominent autism traits later in life⁷. The excess fluid appears as early as 6 months of age and persists through age 3⁹.

What about the structure of the connections between brain regions?
A solid body of evidence suggests that white matter, the bundles of long neuron fibers that connect brain regions, is also altered in people with autism. Researchers typically infer the structure of white matter by using a technique called diffusion MRI, which measures the flow of water throughout the brain.

People who lack all or part of one white matter tract called the corpus callosum, which connects the brain’s two hemispheres, have an increased likelihood of being autistic or having traits of the condition¹⁰. The corpus callosum contains many of the long-range connections that extend throughout the brain; the fact that disrupting those connections may lead to autism traits supports the connectivity theory of autism.

Preschoolers with autism show significant differences in the structure of multiple white-matter tracts, according to a 2020 study. Autistic toddlers and adolescents, too, show alterations in white matter throughout the brain^11,12.

Are there sex differences in the brain structure of people with autism?
It’s unclear. Identifying sex differences in autism remains challenging because fewer girls than boys are diagnosed with autism, says Mark Shen, assistant professor of psychiatry at the University of North Carolina at Chapel Hill.

Still, a few recent studies have turned up hints of sex differences in the brain in autism. A 2020 study showed that the amygdala is more affected in autistic girls than in autistic boys¹³. An enlarged amygdala is associated with more severe emotional problems specifically in autistic girls, according to other work.

White-matter changes in preschoolers with autism also differ by sex: Autistic girls have an increased measure of structural integrity in their corpus callosum compared with non-autistic girls, whereas that measure is lower in autistic boys than in non-autistic boys¹⁴.

Other structural differences, such as the rate of brain growth and amount of cerebrospinal fluid, appear similar between the sexes^6,9.

Why is brain structure in autism important to study?
Because autism is a heterogeneous condition, “when we talk about autism, we’re probably talking about different biological subtypes,” Shen says.

Though not every baby who is later diagnosed with autism will have excess brain fluid at 6 months of age, and not every autistic adult has an underdeveloped corpus callosum, learning more about these subtypes can help researchers develop biologically based treatments for individuals with autism.

Additionally, finding structural biomarkers that can identify subtypes of autism in a noninvasive way, even before autism behaviors can be detected, will help “move the needle earlier” for autism diagnoses, Shen says.

The post Brain structure changes in autism, explained appeared first on Spectrum | Autism Research News.

A quest for Quincy: Gene therapies come of age for some forms of autism

Wed, 14 Oct 2020 11:00:37 GMT

The post A quest for Quincy: Gene therapies come of age for some forms of autism appeared first on Spectrum | Autism Research News.

Book Review: An autistic writer recounts the fun and futility of trying to fit in

Tue, 13 Oct 2020 11:00:00 GMT

Journalist Sarah Kurchak begins her memoir, “I Overcame My Autism and All I Got Was This Lousy Anxiety Disorder,” with a disclaimer: “I do not speak for all autistic people. I will not try to. I do not want to.” With that out of the way, what follows is a superb ‘autiebiography’ — an autobiography written by an autistic person — which, though it may not reflect the experiences of everyone on the spectrum, is sure to resonate with many, myself included.

There is also much in this book for autism researchers — Kurchak extensively cites individual studies, as well as Spectrum. If you have ever wondered how autistic people think about your work and how we use it to understand ourselves, Kurchak provides an enlightening glimpse.

The term ‘autiebiography’ first appeared in the neurodiversity community in the early 1990s. There are now plenty of such books — enough that they can be considered their own genre. The mother of them all was “Emergence: Labeled Autistic,” the 1996 memoir by autism activist and animal science researcher Temple Grandin, which was the basis of a 2010 biopic.

At the time Grandin’s book was published, autistic people were widely thought to be incapable of self-reflection. (Sometimes we still are, although that is, thankfully, changing.) A contemporaneous review in the Los Angeles Times described Grandin as an “exception” and a “recovered autistic.” Of course, many experts now recognize that there is no such thing. People don’t recover from autism. We just learn to muddle on. And that muddling often comes with a cost.

Kurchak, who was not diagnosed with autism until age 27, discusses that cost at length. She notes that autism diagnosis, including her own, is very much ‘fail first’ — people may struggle for years before a diagnosis helps them to understand themselves. And she is forthcoming about her strengths and what she needs to be her best self. Perhaps the most remarkable thing about her memoir is that she is adamant that she is neither an exception nor exceptional. She refuses to be an object of pity.

She is candid about her teenage struggles to fit in with peers in her small hometown in Ontario, Canada. She describes sensory issues that made wearing jeans feel like being encased in sandpaper — a misery she forced herself to tolerate. And she is frank about relationships and sexuality. Some readers may find such frankness uncomfortable. I found it relatable and funny enough that I occasionally choked on my seltzer while reading.

“Do you know how demoralizing it is to be told that boys will f— anything — including, according to one popular movie released at the peak of my humiliation, a pie — when they will not f— you?” Kurchak asks at one point while recounting her teenage misadventures with sex and sexuality, or lack thereof. And yes, I do. I’m a little younger — I was prepubescent when “American Pie” was in theaters. But I remember feeling repulsive and perhaps unlovable as a teenager, and this is perhaps the first time I have read it laid out, plainly and directly, in writing.

Kurchak’s experiences in the workplace are equally poignant and entertaining. Reflecting on her time working in the Canadian music media industry, she writes: “There’s nothing quite like immersing yourself in a culture of obsessive pedants with rigorous filing processes and meticulous records rankings to make you realize that sometimes the line between dedicated and disordered isn’t clear.”

She is similarly enthusiastic about her short stint as a professional pillow fighter. “Work and socialize with people who are arguably less normal than you are,” Kurchak jokingly recommends.

My biggest criticism of “I Overcame my Autism” is that it would have benefitted from more aggressive editing. Sentences are often long and meandering, and at several points, Kurchak lists a series of similar words separated by slashes instead of just picking the one that’s most apt. She is also too quick to apologize: It does not make sense to apologize for failing to represent all autism accurately, as a single person. Memoirs are, by definition, about one person’s experience. That any autistic person somehow represent all autistic people is a ridiculous expectation. Some readers have that expectation, and I think those readers are better left ignored.

Comedian Hannah Gadsby, who is also on the spectrum, provided an enthusiastic blurb for Kurchak’s book, and it’s easy to see why. Like Gadsby’s most recent comedy special, it weaves together humorous anecdotes, jagged honesty and occasionally painful amounts of self-awareness. For me, as an autistic woman, it provided a rare chance to feel seen and understood.

Sara Luterman is a freelance writer whose work has appeared in The Washington Post, The Nation and Vox.

The post Book Review: An autistic writer recounts the fun and futility of trying to fit in appeared first on Spectrum | Autism Research News.

Epidurals linked to slightly higher autism odds, but connection is unclear

Tue, 13 Oct 2020 11:00:00 GMT

Women who receive epidural anesthesia during labor seem to stand an increased chance of having a child with autism, a new study has found¹. But the study was not designed to prove cause and effect and does not suggest that epidurals cause autism.

The prevalence of autism among the children of women who received an epidural is low: 1.9 percent, compared with 1.3 percent among the children of women who did not receive an epidural. That difference corresponds to a 0.6 percent increase in the odds of having a child with autism for the epidural group. The results were published yesterday in JAMA Pediatrics.

Doctors should not consider recommending against epidurals during labor before there is more research on the association, experts say.

“There may be many other factors that could explain that small increase,” says co-lead researcher Anny Xiang, director of biostatistics research in the Department of Research and Evaluation at Kaiser Permanente Southern California in Pasadena.

Such factors — which the study did not account for — could include a family history of psychiatric or neurologic conditions, or differences in the women’s propensity to seek an autism diagnosis for their children, says Brian Lee, associate professor of epidemiology and biostatistics at Drexel University in Philadelphia, Pennsylvania, who was not involved in the work. “The major concern is that there are unobserved characteristics between” women who receive epidurals and those who do not, he says. “It’s quite possible other differences exist beyond that which is seen.”

Linking factors:

Xiang and her team looked at electronic medical records for 147,895 babies born in a network of hospitals in Southern California from 2008 through 2015, noting which of their mothers had received an epidural. They focused on children born vaginally, as some previous studies have linked birth by Cesarean section to autism. All of the children had been screened for autism at 18 to 24 months of age. Pediatric developmental specialists confirmed diagnoses.

The team also collected data on other characteristics in the babies’ mothers that could influence early neurodevelopment, including education level, socioeconomic status, smoking during pregnancy or any pregnancy-related conditions — such as preeclampsia, eclampsia or a fever during labor.

Among 38,176 babies unexposed to an epidural, 485 had been diagnosed with autism by the end of the study period; among the 109,719 babies who were exposed to the anesthesia, 2,039 were diagnosed with autism. After adjusting for race, education, socioeconomic status and pregnancy complications, the researchers found that children in the epidural group were 37 percent more likely to have autism than those in the unexposed group.

The increase in autism likelihood rose among children the longer their mother had an epidural — from 33 percent for fewer than 4 hours, to 46 percent for more than 8 hours. The longer the epidural duration, the greater a woman’s chance of also having a fever, which is associated with elevated autism odds. But the link between epidurals and autism persisted even after the researchers controlled for fever.

The study should not change how pregnant women plan to give birth, says Alex Butwick, associate professor of anesthesiology, perioperative and pain medicine at Stanford University in California, who was not involved in the work. The small increase in autism likelihood is counterbalanced by the benefits of an epidural, including avoiding general anesthesia in the event of an unplanned Cesarean delivery, he says.

Hispanic women are less likely to receive an epidural than are those in other racial groups, as are women from low-income areas, the study found. The researchers also found several other significant differences between women who received an epidural and those who did not in terms of education levels and pregnancy factors.

Untangling causes:

Previous work involving monkeys showed that the drug used in epidural anesthesia can enter an infant’s brain and affect development². But the current study was observational and not set up to determine whether the drug contributes to autism in people.

Epidurals can increase the duration of labor, but previous research suggests that longer labor is not tied to increased odds of autism^3,4.

It is possible that lifestyle and environmental factors that were not measured in this study contributed to the results seen here, Xiang says, or a father’s genetic contribution could also be at play.

The researchers did not account for a common reason that women get epidurals: delivery with forceps or vacuum assistance. “The vast majority of women that go through instrumental delivery have an epidural to provide them with pain relief, because those can be particularly painful experiences,” Butwick says.

The study also did not account for induced labor, which is concerning, Butwick says. That procedure, which previous work has linked to higher odds of autism, often results in more painful labor necessitating an epidural⁵.

For these reasons, Butwick is not convinced that the epidural is a causative factor.

Xiang and her team say they would like to further investigate why longer epidural use is associated with higher autism odds. In some cases, the epidural recipient can control the flow of anesthetic drug, and individual differences in pain tolerance mean that some women will use more than others in a given time period. The researchers plan to mine electronic pharmaceutical records to see whether the dosage of anesthetic, and not just how long someone is on it, affects autism likelihood.

The post Epidurals linked to slightly higher autism odds, but connection is unclear appeared first on Spectrum | Autism Research News.

Brain organoids reveal neuronal flaws in syndrome tied to autism

Mon, 12 Oct 2020 11:00:00 GMT

Neurons derived from people with 22q11.2 deletion syndrome, a genetic condition linked to autism, show deficits in electrical activity and calcium signaling, according to a new study¹. A single gene appears to be largely responsible for these defects, the study shows.

Up to 20 percent of people who lack part or all of the chromosomal region 22q11.2 have autism. Individuals with the deletion may also have schizophrenia, seizures, heart defects, immune dysfunction or learning problems.

The new findings uncover factors that may contribute to the development of psychiatric conditions associated with 22q11.2 deletion syndrome. They could also help researchers identify new therapeutic targets, says lead author Sergiu Pasca, associate professor of psychiatry and behavioral sciences at Stanford University in California.

The syndrome is relatively common, occurring in up to 1 in 4,000 newborns, Pasca says. But researchers do not fully understand how genes in the 22q11.2 region contribute to autism or other conditions, he adds.

Brain signature:

To solve this molecular puzzle, Pasca and his team reprogrammed skin cells from 15 people with the deletion and 15 controls into induced pluripotent stem cells. Using a technique they developed in 2015, they coaxed these cells to turn into neurons, which self-organize in a dish into spherical clusters called organoids. The organoids show some key features of the developing cerebral cortex, a brain region implicated in autism.

The neurons derived from people with 22q11.2 syndrome spontaneously fire four times as frequently as neurons derived from controls, the researchers found. And the electrical activity of the 22q cells does not set off the usual spike in calcium levels, which is crucial for neurons to exchange messages.

In some other syndromes tied to schizophrenia and autism, calcium-channel genes are mutated. But the number of channels and the speed at which they work in 22q neurons is the same as in control neurons. Instead, the 22q cells show an unusually low voltage difference across the cell membrane when they aren’t firing, causing the signaling defects and hyperexcitability, the researchers found.

The researchers suspected that a gene called DGCR8 might be responsible for the neuronal deficits in the organoids because it lies within 22q11.2 and is linked to abnormal electrical activity in the neurons of mice². DGCR8 is essential for the synthesis of short RNA fragments, called microRNAs, that regulate gene expression.

Lowering DGCR8’s expression levels in control neurons reproduced the abnormalities seen in 22q neurons. In contrast, boosting the gene’s activity in 22q neurons or treating them with antipsychotic drugs prevented them from being overly excitable and reversed their calcium-signaling defects. The study was published 28 September in Nature Medicine.

Treatment target:

Previous studies have analyzed lab-grown neurons derived from people with schizophrenia or autism-related disorders such as Rett and fragile X syndromes. But most used only a few human-derived cell lines, says Guo-li Ming, professor of neuroscience at the University of Pennsylvania in Philadelphia. The new study, Ming says, “has a total of 30 human lines — that’s a huge effort.”

By studying brain organoids derived from so many people, the researchers were able to identify the gene that might be involved in the psychiatric conditions associated with 22q11.2 syndrome, says Sally Temple, scientific director of the Neural Stem Cell Institute in Rensselaer, New York. “Whenever we have a light shining ahead, saying, ‘This is what you should really be looking at,’ it means that we’re making progress,” she says.

The study participants with 22q11.2 syndrome vary in their psychiatric diagnoses, and yet all the brain organoids derived from their cells show the same neuronal abnormalities. “That’s somewhat surprising, because we know there are a lot of differences in the genetic background of different people,” Ming says.

The deletion might conspire with other factors to ultimately determine which psychiatric conditions a person has, Pasca says. “It could be that the deletion causes cellular defects, and once there is a stressor such as social stress, disease develops.” It’s also unclear whether these cellular defects are related to the high prevalence of seizures in people with 22q11.2 syndrome, he says.

The hallmarks of most neuropsychiatric conditions can change over time, says Giuseppe Testa, director of the stem cell epigenetics unit at the European Institute of Oncology in Milan, Italy. Studies that look at a larger number of people with 22q11.2 deletion syndrome or other neurodevelopmental conditions could help to elucidate the relationship between the neuronal defects observed in the lab and the psychiatric manifestations of the conditions, Testa says. The new study, however, is a “great resource” for understanding how the 22q11.2 deletion contributes to schizophrenia and autism, he says.

Pasca’s team is trying to pinpoint molecules that could open new therapeutic avenues for 22q11.2 deletion syndrome. The antipsychotics they tested restore the unusual voltage differences in the 22q neurons, but they don’t address the core mechanisms responsible for psychiatric conditions linked to the syndrome, Pasca says.

What’s more, antipsychotics have many side effects, and not all individuals respond to them, he says. “We need better therapies — we need to identify what the key molecular players are and target those.”

The post Brain organoids reveal neuronal flaws in syndrome tied to autism appeared first on Spectrum | Autism Research News.

How the striatum is linked to autism

Fri, 09 Oct 2020 11:00:50 GMT

The repetitive behaviors seen in autism may originate in the striatum, a cluster of neurons involved with initiating and executing movements. Studies also hint that this ‘reward hub’ in the center of the brain underlies some of the condition’s social difficulties and is essential for learning what sensory input deserves our attention.

In this video, David Sulzer, professor of neurobiology at Columbia University, and Ori Lieberman, a graduate student at the university, explain the research.

Read or listen to the related article here.

The post How the striatum is linked to autism appeared first on Spectrum | Autism Research News.

Social motivation predicts language skills in autistic children

Thu, 08 Oct 2020 11:00:00 GMT

The more autistic children tune in to and communicate with others as toddlers, the stronger their conversation skills are later in childhood, according to a new study¹.

The findings lend support to the social motivation theory of autism, which posits that some autistic children do not prioritize social cues or seek out social interactions and, as a result, miss out on opportunities to practice and develop language skills.

The work suggests that parents and clinicians should aim to enhance an autistic child’s social motivation rather than focusing on helping them develop a particular skill, says Emily Neuhaus, assistant professor of psychiatry and behavioral sciences at the University of Washington in Seattle, who was not involved in the study.

Social motivation leads to better expressive language, or the ability to communicate thoughts and ideas, in two ways: by pushing children to try to communicate and encouraging them to tune in to the communication of others, the researchers found.

Just one of the factors is not sufficient for better language skills, the study found; “it has to be both,” says study investigator Pumpki Lei Su, a postdoctoral researcher at the University of Delaware in Newark. “And it’s not just a one-way street,” she says.

The findings support a theory of language development that is self-reinforcing: The more a child tries to communicate, the more she elicits communication from others; and the more input she gets from others, the more she tunes in, which helps hone her expressive language, Su says.

Top model:

Su and her colleagues analyzed data from another study that used parent reports of social and communication skills in 87 autistic children over two years, starting when the children were 14 to 31 months of age².

The team saw a strong connection between the children’s social motivation scores on their earliest tests, as measured by the ‘Social Approach’ subscale from the Pervasive Developmental Disorder Behavioral Inventory, and their expressive language skills two years later, assessed using the Mullen Scales of Early Learning (MSEL).

There are three theories that could account for how early social motivation leads to better expressive language: Autistic children who are socially motivated try to communicate more frequently than their peers; the link is driven by strong receptive language skills, or the ability to tune in to someone else’s words and gestures; or both^3,4,5.

The researchers set up three statistical models to test these theories, using additional previously collected data on how frequently the children tried to communicate with others, as measured by a short play-based test called the Early Communication Index, and their receptive language skills, measured using the MSEL.

The model that included both intentional communication and receptive language explained the data best, says lead researcher Paul Yoder, emeritus professor of special education at Vanderbilt University in Nashville, Tennessee. The study was published in Autism in September.

Additional input:

Identifying early life skills that could be targeted to improve later functioning “is an incredibly important thing,” says Thomas Frazier, professor of psychology at John Carroll University in University Heights, Ohio, who was not involved in the study.

But he says he has some concerns about how the different behaviors were measured.

“My biggest worry is that they’re not actually measuring social motivation in the purest form, and really what they’re measuring is social motivation and social communication,” he says.

If the parent reports do not distinguish between motivation and communication, then social-communication abilities early in life, rather than social motivation, may drive the expressive-language skills they evaluated later on.

If the findings hold, however, “then maybe we should look at treatments that focus on increasing social motivation biologically as well as behaviorally,” Frazier says. One way to do that is through drugs such as oxytocin or vasopressin that act on the brain’s reward system and have been shown to improve social motivation.

Yoder and his colleagues are trying to replicate their findings with a new group of autistic children and adding in a measure for the parents. They want to see how a parent’s communication affects the child’s receptive language and, ultimately, the child’s ability to express herself.

The post Social motivation predicts language skills in autistic children appeared first on Spectrum | Autism Research News.

Virtual lab visits enable remote assessments of child development

Wed, 07 Oct 2020 11:00:00 GMT

A new telehealth test offers researchers a way to measure a child’s development and detect signs of atypical behavior remotely¹. It could help them recruit more people for their studies and adjust their methods to a socially distant world.

Autism researchers generally assess children in person. This means families participating in research often must travel, which can be costly and time-consuming and present a barrier for those living in rural areas or who have children with challenging behaviors.

Researchers have been pushing for telehealth-based approaches in order to improve access. Since the start of the coronavirus pandemic, scientists have also had to quickly adapt their studies to online or virtual formats.

But most telehealth approaches allow researchers to gather only certain types of data. Researchers can use videos to observe a child’s behavior following specific stimuli, for example². Or they can use wearable devices to passively track biomarkers, such as vocalizations or heart rate, gathering data on broad patterns of activity.

The new assessment — called the Parent-Administered Neurodevelopmental Assessment, or PANDABox — enables researchers to monitor biomarkers’ responses to specific stimuli, a method commonly used in the lab to pick up on potential signs of autism. It consists of a standardized protocol and set of tools to collect lab-grade data on infants’ behaviors and biomarkers at home.

PANDABox could help make research more cost-effective and accessible to a greater diversity of people, “not just those with enough privilege and resources to come to us,” says Bridgette Kelleher, associate professor of psychological sciences at Purdue University in West Lafayette, Indiana, who led the research.

The remote assessment could also help researchers get a more realistic snapshot of children’s behaviors, because children may act differently in a lab than they do at home.

Remote recording:

Researchers start by sending a caregiver a ‘PANDABox’ containing the necessary equipment, such as a computer pre-loaded with slides and software, a heart-rate monitor, a wearable vocal recorder, a webcam and a variety of toys.

At the time of a test, a researcher coaches a caregiver, over the phone and via video conference, on how to set up the equipment. The researcher then guides the caregiver through a series of tasks to test a child’s developmental skills. Such tasks can include having the child watch a video or play with a toy, or having the caregiver read the child a book.

During the test, the webcam, heart-rate monitor and vocal recorder capture data, which the researchers can synchronize later with the timing of the tasks. Once the testing is complete, the caregiver sends the box back.

Researchers tested PANDABox on 16 infants with Down syndrome, aged 5 to 19 months. For each assessment, research assistants gauged whether the infants were engaged in tasks and rated how well the parents administered tasks, compared with research standards in the lab. The team also had caregivers complete an anonymous survey about the experience, rating their level of satisfaction with privacy, ease of use and other aspects of the assessment.

Almost every family rated PANDABox highly — they described their satisfaction level as “good” or “excellent” on 97 percent of the survey questions, the researchers reported in July in Frontiers in Psychology. Infants also took well to the test: Although fussiness and fatigue are common problems during assessments, the children remained engaged throughout nearly all of the PANDABox tasks.

In addition, caregivers administered 94 percent of the tasks with only minor deviations from the standardized protocol. Overall, these findings suggest that, with guidance, caregivers are capable of collecting high-quality data, the researchers report.

Data loss was also generally low, although 25 percent of the heart-rate data were absent and 13 percent were partially missing, largely due to programming errors. Because such errors should be preventable, data loss rates may improve in the future, the researchers say.

The post Virtual lab visits enable remote assessments of child development appeared first on Spectrum | Autism Research News.

Why it is imperative to ask autistic adolescents about bullying

Tue, 06 Oct 2020 11:00:00 GMT

Adolescents with autism are more likely than their neurotypical peers to experience bullying¹. They are also more likely to have suicidal thoughts and behavior².

We know that bullying contributes to suicidality in typically developing adolescents. When the news covers a young person’s tragic death by suicide, bullying is often mentioned. This anecdotal evidence is borne out by research: Young people who experience bullying are 1.4 to 10 times as likely to develop suicidal thoughts or behavior as their non-bullied peers are³.

Most of the time, having suicidal thoughts and behaviors goes hand in hand with having a psychiatric condition, something that is also more common among adolescents with autism than among typically developing children. But not all people who are diagnosed with a psychiatric condition experience suicidal thoughts or behavior. The higher incidence of co-occurring psychiatric conditions in adolescents with autism may reflect an underlying biological vulnerability, or the fact that they are exposed to more stressors than are their typically developing peers.

In a new study, we controlled for the presence of co-occurring psychiatric conditions and other possible confounders that could influence suicidality independently of bullying. We found that adolescents with autism who experienced bullying were still twice as likely as those who did not to later develop suicidal thoughts and behavior⁴.

Our findings underscore the critical importance of identifying and preventing bullying among autistic youth. Bullying must be viewed as a negative outcome for children with autism, and not accepted as something for which there is no solution.

Real risk:

We examined the clinical records of 680 autistic adolescents who had been referred to a mental health clinic in South London, England. We focused on adolescents who were not suicidal at their initial visit.

At that first assessment, 30 percent of the adolescents in our sample reported having been bullied by peers. They were nearly twice as likely as those who did not report bullying to go on to have suicidal thoughts or behaviors during the next five years.

Our findings could support a number of causal theories of suicidality. One we feel is clinically helpful is the interpersonal theory of suicide, which suggests that a combination of three factors leads to suicidal behavior: thwarted belongingness, ‘perceived burdensomeness’ and acquired capability.

Belongingness is our sense that we are accepted by others. Being married, having children and having many friends are all associated with lower rates of suicide. It is easy to understand how being bullied by one’s peers might negatively impact upon one’s sense of belonging. Being bullied can also exacerbate ‘perceived burdensomeness,’ which is the belief that others or society would be better off without you.

Young people who experience bullying may also become habituated to painful experiences and, as a result, feel less fear of death than do other young people. This sort of desensitization leads to an acquired capability for suicide, which is necessary for suicidal thoughts to be acted upon.

A call to action:

In our experience, clinicians who see autistic adolescents may regard bullying as so pervasive that it’s hardly worth commenting on.

We urge clinicians to fight this tendency and make a concerted effort to ask children with autism about bullying. And when a young autistic person reports bullying to mental health professionals, it needs to be taken seriously. Our research suggests that bullying not only contributes to suicide risk but also impacts young people’s treatment trajectories.

Most clinical services involve scheduled assessments that outline what essential information clinicians should collect during their sessions with young people. We suggest that information about bullying should be added to these assessments. Some adolescents may not feel comfortable sharing information about bullying with a professional they’ve only just met, but by asking about it early on — for example, simply asking, “Do you feel anyone is being really mean to you at the moment?” — we can make it clear that it’s something appropriate for them to talk about with their clinician. When information about bullying is difficult to collect from the young person directly, clinicians should query family members, caregivers or schools.

Teachers have a key role to play. In school settings, evidence suggests that intensive anti-bullying interventions in which teachers meet with parents are most effective⁵. Schools can also benefit from autism-specific anti-bullying strategies, including ‘befriending interventions,’ which help autistic children form friendships with typical peers. Schools should use robust evaluations to assess the effectiveness of such interventions and involve young people with autism in the development of their anti-bullying policies. Although moving schools should be a last resort, it is sometimes necessary. These moves should be well planned with input from the prospective school and clinician. Schools are normally keen to help early; they generally want to ensure a successful transition for new students.

For autistic adolescents remaining at their school or moving to a new one, clinicians and teachers should focus on creating interventions that enable them to develop a sense of belonging and to identify the value they bring to the people around them. In fact, these approaches can be applied to all students as a universal approach to prevent bullying. Clinicians also need to support school leaders to sustain their anti-bullying strategies; it should always be a ‘live’ issue within their local schools. In our experience, schools really value local clinicians providing advice to their school leadership, especially when advocating for regular awareness campaigns on the serious consequences bullying can have on the mental health of young people, and the need to provide targeted approaches to support those with autism.

In addition to school-based bullying, cyberbullying is an emerging concern. Further research is needed, as we suspect that young people with autism may not be equally affected by all forms of bullying. The majority of cyberbullying prevention efforts focus on educating young people, their teachers and their parents to recognize and report it.

The latest version of the Long Term Plan issued by the United Kingdom’s National Health Service calls upon mental health professionals to look beyond their consulting rooms and think about mental health efforts in communities. Bullying prevention initiatives are often left to schools or websites. Given the serious consequences bullying has on mental health, however, mental health professionals should play an active role in developing and evaluating anti-bullying initiatives.

Johnny Downs is senior clinical lecturer in the child and adolescent psychiatry department at King’s College London in the United Kingdom, and honorary consultant at the South London and Maudsley NHS Foundation Trust. Rachel Holden is a clinical psychologist at the South London and Maudsley NHS Foundation Trust.

If you or someone you know is having suicidal thoughts, help is available. Click here for a worldwide directory of resources and hotlines that you can call for support.

The post Why it is imperative to ask autistic adolescents about bullying appeared first on Spectrum | Autism Research News.

Nighttime light affects sleep, repetitive behaviors in autism mouse model

Mon, 05 Oct 2020 11:00:00 GMT

Mice missing the autism gene CNTNAP2 sleep more at night, when they should be active, and groom themselves more than usual when exposed to light at night, according to a new study. Both disruptions disappear when the mice are given the sleep hormone melatonin¹.

The findings suggest alterations in the gene relate to a vulnerability to sleep disturbances, says lead investigator Christopher Colwell, professor of psychiatry at the University of California, Los Angeles.

Many people with autism struggle to fall and stay asleep. Lack of sleep can exacerbate some challenges associated with the condition, including repetitive behaviors and social difficulties.

Autistic people may also have unique susceptibilities to sleep disruptions from artificial light, some research shows^2,3. Light from sources such as streetlamps or electronic screens at night interferes with the body’s 24-hour ‘clock,’ known as the circadian rhythm, which regulates patterns of gene expression, hormone levels, slumber and other functions⁴.

Clinicians often prescribe melatonin, a hormone that induces sleep in response to darkness, to people with autism, including children. The new findings suggest that melatonin can also ease some autism traits and that lighting considerations may be important for children with autism or other neurodevelopmental conditions, Colwell says.

“Lighting conditions may be even more important than we have appreciated,” he says. “I think this is low-hanging fruit in terms of management. This is about improving the quality of life.”

Behavior changes:

Colwell and his team examined sleep patterns, social activity and repetitive behaviors in mice missing both copies of the gene CNTNAP2. In people, mutations in this gene are associated with autism, language impairments and changes in brain connectivity.

Under typical lighting conditions — 12 hours of daylight and 12 hours of darkness — the knockout mice were less active at night, when mice are usually awake, than control mice. They also had small differences in their sleep patterns and in their circadian rhythms, based on patterns of gene expression and neural activity.

The knockout mice groomed themselves more frequently, an activity considered akin to repetitive behaviors in autistic people. The animals were also equally interested in interactions with an object and with a new mouse, whereas control mice preferred to engage with another mouse.

The patterns changed after researchers exposed some mice of each type to a dim light, about the brightness of a night light, all night long.

Both the CNTNAP2 mice and the controls exposed to nighttime light slept more at night than their undisturbed counterparts. They also showed lowered social interest: The knockout mice preferred an object, whereas the controls showed equal interest in the object and another mouse. Self-grooming increased in the night-light-exposed knockouts only.

The researchers also examined patterns of gene expression and electrical activity in neurons from the mice’s suprachiasmatic nucleus, a brain region that regulates circadian rhythms. Normally, these patterns differ between day and night, but cells from both knockouts and controls exposed to light largely lost this diurnal distinction. Nighttime light had a greater effect on cells from the knockout mice than on those from typical mice.

Giving night-light-exposed knockout mice an evening dose of melatonin decreased their excessive grooming behavior and increased their nighttime activity in general. Giving the mice melatonin in the morning was not effective, which highlights the importance of normalizing the circadian cycle, Colwell says. The findings were published in Neurobiology of Disease in September.

Other models:

After two weeks without light exposure at night, both control and knockout mice returned to their usual patterns and behaviors, suggesting the effects are temporary. Future research should examine whether there are developmental periods in which light exposure and sleep disruption lead to more permanent changes, Colwell says.

The experiment does not perfectly mimic how light at night may affect sleep in people, says Philippe Mourrain, associate professor of psychiatry and behavioral sciences at Stanford University in California, who was not involved in the research. Exposure to light pauses melatonin production in people but does the opposite in mice.

The researchers also exposed the mice to constant light all night, but most people encounter it only sporadically — when using a device before bed, for example.

Still, the findings demonstrate the importance of normalizing not just sleep, but also circadian patterns, Mourrain says.

“It shows that circadian defects per se, without regarding any sleep defects, are already important for the autistic trait,” he says. “But if you really want to understand how to improve children’s health during development in terms of sleeping well at night, you need to take both into account, and mice cannot allow you to model that.”

Of note, the study is among the first to attempt to understand the causal relationships between sleep and severe autism traits, says Olivia Veatch, assistant professor of psychiatry and behavioral sciences at the University of Kansas, who was not involved in the work. Thus far, researchers have been unsure whether severe traits prevent sleep or lack of sleep exacerbates existing difficulties — or perhaps both things take place in a cycle.

The mouse model the researchers used does not naturally produce melatonin, so it’s interesting that the hormone would have any effect, she says.

“It’s just definitely not as straightforward as you would hope,” Veatch says. “But this is a step in the right direction toward teasing out what is actually causing sleep problems in individuals who have genetic mutations that are risk factors for autism.”

Melatonin can improve sleep in children with autism even when they already have the typical levels of melatonin, indicating that the hormone may have important functions beyond sleep, such as reducing anxiety, Veatch says⁵.

“We need to figure out what [else] melatonin does,” she says.

The researchers next plan to examine whether different colors of light have different effects. The blue wavelengths of electronics, for example, can boost attention and energy, which is good during the day but particularly harmful for bedtime, studies show. They are also investigating the role of brain inflammation in disrupted sleep.

The post Nighttime light affects sleep, repetitive behaviors in autism mouse model appeared first on Spectrum | Autism Research News.

Autistic toddlers do not tune in to sounds with others

Fri, 02 Oct 2020 11:00:00 GMT

Unlike typical toddlers, those with autism tend not to share experiences involving sound — dancing to music with their parents, for example, or directing a parent’s attention toward a cat’s meow — according to a new study¹.

Sharing sounds in this way is a form of joint attention — focusing on something intentionally with another person — which helps young children learn social skills and how to communicate. Joint attention also occurs when, for instance, a parent looks at a toy and names it, and their child follows their gaze to look at it, too. Children typically develop joint attention as toddlers, but autistic children often do not, and a lack of that skill is thought to be one of the earliest signs of autism.

Previous work has focused on visual joint attention, often in the context of a parent trying to get a child to look at their face or at a particular object. The new study examined joint attention elicited by a range of sounds. As with new sights, children with autism are often interested in new sounds, the researchers found, but less interested in sharing them.

This work is one step toward finding out how variations in children’s experiences of sharing sounds might relate to later language development, says lead researcher Lauren Adamson, Regents professor emerita at Georgia State University in Atlanta. The findings were published in August in Autism Research.

Some past work has led researchers to suspect that atypical face processing lies at the root of autistic children’s joint-attention problems, because joint attention often depends on a child following a parent’s gaze. The new findings point to a deeper cognitive construct involved in atypical joint attention, one that is likely shared by visual and auditory processing, says Peter Mundy, professor of education and psychiatry at the University of California, Davis, who was not involved in the work.

“That’s very useful, because we get stuck in a paradigm if we think about it being tied specifically to a behavior rather than a neurocognitive process,” he says.

Sharing sounds:

Adamson and her team examined auditory joint-engagement skills — joint attention coupled with an interaction around a shared experience — in 49 typically developing toddlers, 46 autistic toddlers and 46 non-autistic toddlers with other developmental disabilities, such as developmental language disorder. All of the children were younger than 30 months old.

While each child played with a parent or caregiver, the researchers used hidden speakers to pipe in a series of different sounds: instrumental classical music, birdsong or cats meowing, train or motorcycle sounds and recordings of human speech that included the child’s name.

At first, the researchers instructed parents to ignore the sounds and continue playing, giving them the opportunity to see if the children noticed a sound and attempted to share it, perhaps by looking back and forth between the parent and the sound source, talking to the parent about the sound or looking at the parent and pointing toward the sound source.

For all of the non-human sounds, most toddlers in all of the groups noticed the sounds and then turned or pointed toward their source. Some autistic toddlers noticed the sounds — they stopped playing or their eyes widened, for example — but did not look toward them.

When the children heard the sound of someone speaking, however, a significant difference emerged: The autistic children were less likely than the other two groups to notice or to orient toward the voice, even when it called their name. And only 15 percent tried to share any of the speech sounds, compared with 73 percent of the typical children and 41 percent of those with other developmental disabilities.

The researchers observed less of a difference between groups when they played the sounds a second time and asked the parents to try to get the child’s attention and share the sound by pointing toward it, naming the animal or machine they heard or dancing with the child along to the music. Among the typical toddlers, 98 percent shared at least one sound with their parent during this phase, compared with 91 percent of those with developmental disabilities and 70 percent of the autistic children.

“There are some children who can share the sounds when adults are attempting to have them share the sounds, but children with autism rarely attempt to share the sounds on their own,” Adamson says.

New paradigm:

Expanding the scope of joint-engagement research to sounds opens the door to new forms of early identification of autism, Mundy says. And it could help researchers home in on which brain areas are involved in both auditory and visual joint engagement, he says.

The new work also suggests that autistic children miss out on valuable cues from parents that would help them learn new words, which could have clinical implications.

The researchers also assessed how the children shared a sound and whether that showed they understood its meaning — looking around for a cat or saying “meow,” for example. By this measure, autistic children exchanged significantly less information with their parents during joint attention than typical children did.

“The fact that autistic children had difficulty engaging around sound, even with their parents’ support, is important to think about in this regard,” says Kristen Bottema-Beutel, associate professor of teaching, curriculum and society at Boston College in Massachusetts, who was not involved in the work.

Looking at joint attention to sounds in this way can reveal which kinds of interactions are particularly challenging for autistic children and help clinicians devise new ways to support them as they learn language, Bottema-Beutel says.

“Interacting together around sounds requires communication — there is no alternative way to jointly engage with them other than communicating about them, or responding to someone else’s communication about them,” she says.

The post Autistic toddlers do not tune in to sounds with others appeared first on Spectrum | Autism Research News.

Autism shares brain structure changes with other psychiatric conditions

Thu, 01 Oct 2020 11:00:00 GMT

Autistic people share some brain structure differences with people who have other neuropsychiatric conditions, including schizophrenia and attention deficit hyperactivity disorder (ADHD), according to a massive new brain-imaging study¹. These shared differences stem from the atypical development of one particular type of neuron, the findings suggest.

The results provide “further evidence that our understanding of autism can really be advanced by explicitly studying autism in the context of other disorders,” says Armin Raznahan, chief of the Section on Developmental Neurogenomics at the U.S. National Institute of Mental Health in Bethesda, Maryland, who was not involved in the study.

The researchers looked at brain scans from 28,321 people to identify structural changes associated with any of six conditions: autism, ADHD, bipolar disorder, major depressive disorder, obsessive-compulsive disorder and schizophrenia.

The team found that the brains of people with these conditions differ from controls in a specific way: They have similar patterns of thickness across the cortex, the brain’s outer layer. The cortical regions with the biggest differences in thickness are typically rich in a particular type of excitatory neuron.

“We were able to put our fingers on what might be behind that commonality,” says lead researcher Tomas Paus, professor of psychology and psychiatry at the University of Toronto in Canada. “That was very exciting.”

The work combined data from 145 cohorts within the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, an international group of researchers who collect and analyze brain-scan data in a standardized way so that they can pool their results.

This collaboration enabled the researchers to draw comparisons between conditions that are more often studied individually, says study investigator Yash Patel, a graduate student in Paus’ lab.

Linking conditions:

Paus, Patel and their colleagues used magnetic resonance imaging (MRI) to scan the brains of 12,721 people with any of the six conditions and 15,600 controls, all aged 2 to 89 years. For each scan, they divided the cortex in the left hemisphere into 34 different regions and assessed the thickness of each. They then looked at how much the thickness in people with any of the six conditions deviated from that of controls.

The same general pattern held for people with any of the six conditions: Regions that were atypically thick or thin in the brains of people with one condition were also atypically thick or thin in the other conditions.

The conditions that were more similar in their patterns of cortical thickness were also more likely to be genetically similar (a measure assessed in a previous study²). For example, autism and schizophrenia, conditions that share genetics and traits, showed the strongest correlation. The new work was published in JAMA Psychiatry in August.

Looking at the same 34 brain regions in the Allen Human Brain Atlas, a repository of gene-expression data, the researchers examined how 2,511 genes are usually expressed in typical brains. To guess at the cell types present in each region, they searched for these genes in expression data of nine different types of cells previously identified in mouse brains³. (Most human datasets that could be used for this purpose do not capture genetic information about a cell’s dendrites, the branches that receive input from other neurons, which are of particular interest for studying development⁴.)

Regions with the most atypical thickness, they found, show high expression of genes associated with a type of pyramidal cell — an excitatory neuron with bushy dendrites.

Developing theories:

Using the BrainSpan atlas, which includes gene-expression data from human brain tissue at 8 weeks postconception to 40 years of age, the team examined how the expression of genes important for pyramidal neurons changes throughout development. They found that the genes in question fall into two groups: those expressed prenatally and those expressed postnatally.

The set of prenatal genes is associated with neurodevelopmental processes, such as the formation of dendrites and the growth of axons, neuronal branches that send signals to other cells in the brain. The other set, expressed after birth, is linked to brain plasticity and synaptic signaling.

Together, the findings hint that the thickness changes seen in the six conditions relate to something atypical happening with pyramidal neurons during two periods of development — first in the womb and then again during a person’s life, Paus says.

Probing these genetic associations in more detail may reveal “specific developmental windows that would be optimal for intervention,” says Carrie Bearden, professor of psychiatry and biobehavioral sciences at the University of California, Los Angeles, who was not involved in the study.

Moving forward, Paus and his colleagues will continue working with the same ENIGMA cohorts, and possibly a few more. They plan to run a similar study to see how cortical surface area, rather than thickness, compares across the conditions. Whereas the thickness of the cortex changes with age, surface area is relatively stable by about 2 years of age, Paus says. For that reason, looking at surface area could provide a glimpse at biological changes that unfold during the earliest years of development.

The post Autism shares brain structure changes with other psychiatric conditions appeared first on Spectrum | Autism Research News.

How scientists secure the data driving autism research

Wed, 30 Sep 2020 11:00:00 GMT

The post How scientists secure the data driving autism research appeared first on Spectrum | Autism Research News.

Beyond the bench: A conversation with Tony Zador

Tue, 29 Sep 2020 11:00:00 GMT

When Tony Zador is thinking about the brain, he’s often exercising his body. A professor of neurosciences at Cold Spring Harbor Laboratory in New York, Zador has run five miles a day, seven days a week since he was 18. “That’s when the ideas sort of click into place,” he says.

His bagel-fueled afternoon jaunts have continued unabated during the coronavirus pandemic, helping to drive forward his research on how the brain’s disparate parts give rise to the complexity of human behavior and experience. Zador’s lab created a brain-mapping technique known as BARseq — an update to the earlier MAPseq — that can trace connections and gene expression in individual neurons. The tool may help researchers understand how brains are connected differently in autistic people.

Spectrum spoke to Zador about the enigma of the human brain, the ‘aha’ moments of running and why a ski resort is a good place for a scientific conference.

Spectrum: What question drives your research?

Tony Zador: Ultimately, it’s: How do you go from three pounds of brain to thought? We know an awful lot about the parts that make up brains — the neurons, the synapses, the molecules — and in spite of all that, we don’t know how to put the pieces together to form a simple, coherent model of how that gives rise to thought and emotions and actions and memories. It’s really frustrating, because it’s like you’ve got a bunch of Tinkertoys and you know that you have all the right pieces, and you don’t know how to put them together quite right.

There’s a great cartoon of a bunch of Scrabble tiles, and the caption is something like, “I just bought a book from Ikea.” That’s kind of how I feel. We understand so much about the pieces, and yet we don’t know how to put them together in quite the right way.

S: Is there a person you’d like to work with whom you haven’t worked with yet?

TZ: I’m really lucky that I have super smart people in my lab, but I also collaborate all the time with all sorts of people who later become friends or who were already friends. Just now I’m really excited because I’m just starting a grant with Ed Boyden. We’ve been friends for years and talking about doing something together, and so now it looks like we can maybe do something that brings our technologies together and will allow us to do things that we wouldn’t otherwise be able to do.

S: What does your daily routine look like?

TZ: My days aren’t that different now during COVID-19, except that the meetings, instead of being face to face in my office, are over Zoom. I have kids, so my daily routine used to start with being woken up earlier than I would like, to get my kids off to school, but now I get to sleep in a bit more. Usually I try to put off my meetings so I don’t have them first thing, and I answer emails or maybe even think a little, but that’s rare. Mostly I don’t have time for that.

I occasionally have some time to work on reviewing papers, writing papers, writing grants, all those things. I don’t have great study habits, so I’m not very efficient, and an awful lot of my time when I’m supposed to be doing something in particular is spent procrastinating and not doing it. Sometimes I go down scientific rabbit holes, and in some sense that’s inefficient but probably good in the long run, because those are when I get excited about new ideas.

I run pretty much every day. I use that time to relax but also often to think through scientific things. Especially if I’m doing something math-related, which is a lot of what I do, that’s when those ideas sort of click into place. If I’m stuck on something I go for a run, and when I get back I at least have an idea of what I should do next.

S: When and where are you most productive?

TZ: It depends. There are different stages of any project. For me, the creative time is at night — I’m a night owl. I get so little sleep because I wait until everyone is asleep, including the kids, and then I work until 2 or 3 a.m. That’s when I get most excited about tracking down ideas. That’s not necessarily when I’m most productive in terms of writing sentences for a paper or something. That is more like a couple of hours after I’ve woken up. But that assumes that I’m productive, which I’m really not these days.

Different people have different styles. I’ve basically come to realize the trick is to embrace what you might think are your weaknesses as your strengths and find collaborators who complement your weaknesses. My strength is that I get excited early on in a project when the project is just being conceived. I love the excitement of doing something new. Once I come remotely close to mastering anything, I kind of start losing interest in it.

S: Do you have a favorite conference?

TZ: I’ve actually started a bunch of conferences, so they’re among my favorites. When I was a postdoctoral researcher I started a conference called NIC, which was Neural Information and Coding. It was a small, invitation-only conference that was always at a ski resort. We would have meetings in the morning, then ski throughout the day, and then meet again in the evening. That eventually grew into a much larger conference called Cosyne — Computational and Systems Neuroscience — which has ballooned up to almost 1,000 people.

The most fun meetings are the smallest meetings. It’s exactly the meeting I wish had been around when I was a graduate student or a postdoc.

I just started a new meeting for neuroscience and artificial intelligence, NAISys. It was going to be held at the end of March, and it was postponed until mid-November. It will bring together people interested in what real brains can tell us about how to build better artificial neural networks.

S: What are you reading right now?

TZ: You mean other than countless papers on immunology because of COVID? I’m reading several books. One is called “Other Minds,” by Peter Godfrey-Smith. It’s all about how smart octopuses are, and how they’re like this weird alien intelligence. Even though I’m a neuroscientist, I knew almost nothing about octopuses. They’re really smart, and the way their nervous system is organized is really different. Related to that, I just finished a book called, “Are We Smart Enough to Know How Smart Animals Are?” by Frans de Waal. It’s just spectacular.

I was an M.D.-Ph.D., and even though I didn’t go on to do a residency, the book all medical students had to read was a novel by a guy named Samuel Shem called “The House of God.” It captured deep truths about what it’s like to be a medical intern. It’s basically a somewhat fictionalized year in the life of a medical intern at MGH, which stood for Man’s Greatest Hospital. Fairly recently, he came out with a sequel called “Man’s Fourth Best Hospital,” and I just started reading that, so I’m excited.

S: What do you eat or drink while you’re working?

TZ: I drink endless cups of coffee, and because I can’t run on a full stomach, and it takes a very long time after eating for me to not have a full stomach, I basically eat bagels until I go for a run. So the answer is coffee and bagels.

The post Beyond the bench: A conversation with Tony Zador appeared first on Spectrum | Autism Research News.